DESCRIPTION: Retinoids regulate a remarkably broad range of biological processes in both developing and adult individuals. The diversity of these effects is matched by the functional complexity of the retinoid receptors. The three types of retinoic acid receptors (RARs) and three types of retinoid X receptors (RXRs) bind at least five distinct types of retinoic acid response elements (RAREs) as either RAR/RXR heterodimers or RXR homodimers. The investigators have recently expanded the diversity of the retinoid response by identifying RIP14 as a seventh retinoid-activated receptor. We hypothesize that RIP14 plays an important, tissue-specific role in retinoid signaling and propose 4 specific aims to further characterize its activities and test this hypothesis. 1) The RIP14 gene will be isolated, and the molecular basis for the expression of the RIP14 isoforms determined. 2) RIP 14 DNA binding sites will be characterized in detail and their ability to confer response to individual isoforms will be defined. 3) The response of the PLTP gene to RIP14 will be critically tested, and other potential RIP14 targets will be identified and characterized. 4) ES cell lines defective in the RIP14 gene will be generated and used to create mice deficient in RIP14.